Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.

Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit. Am J Respir Cell Mol Biol. 2020 Oct 23;: Authors: Linssen RS, Chai G, Ma J, Kummarapurugu AB, van Woensel JBM, Bem RA, Kaler L, Duncan GA, Zhou L, Rubin BK, Xu Q Abstract Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress e.g. by the release of reactive oxygen species (ROS) and myeloperoxidase (MPO) during NETs formation in the airways would increase mucus viscoelasticity. We collected human mucus from endotracheal tubes of healthy patients admitted for elective surgery and co-incubated these samples with NETs from PMA- stimulated neutrophils. Unstimulated neutrophils served as controls and blocking experiments were performed with dornase alfa for extracellular DNA and the free radical scavenger dimethylthiourea (DMTU) for oxidation. Compared to controls, the co-incubation of mucus with NETs resulted in 1) a significant increase of the mucus viscoelasticity (macrorheology), 2) significantly decreased mesh pore size of the mucus and decreased movement of muco-inert nanoparticles through the mucus (microrheology) b...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research